Diabetes is one of the serious global issues. Approximately 285 million people are affected by diabetes worldwide. Up to 25% of diabetic patients develop diabetic foot ulcers that lead to poor quality of life and the risk of lower-extremity amputation. The current methods for clinical treatment of diabetic wounds including glycemic control, debridement, removing infectious agents, moisture dressings, and offloading high pressure from wounds may facilitate would closure, but there is no efficient treatment strategy for all patients with diabetic wounds. Some patients failed to heal using these standard approaches. This indicates that the fundamental and molecular events of impaired wound healing are in need for further investigations.
Wound healing is a complicated biological process that can be divided into four overlapping phases: hemostasis, inflammation, proliferation, and tissue remodeling. In hemostasis phase, platelets aggregate and quickly trigger fibrin clot formation that can protect wounds and prevent bacterial invasion after cutaneous wound injury. Inflammatory phase begins within 2-3 days. Leukocytes, such as neutrophils and macrophages, are attracted to wound lesions by chemokines secreted from injured tissues. Recruitment of leukocytes also participates in clearance of invasive pathogens and induction of inflammatory response by production of inflammatory cytokines. The process of neovascularization concurrently occurs with the proliferation of fibroblasts and keratinocytes and the deposition of extracellular matrix in proliferation phase. Finally, several events occur in tissue remodeling phase, including the appearance of myofibroblasts, extracellular matrix remodeling, and scar formation.
Tumor endothelial marker 1 (TEM1), also known as endosialin or CD248, is initially identified as a highly up-regulated protein in tumor vasculature. TEM1 consists of six domains, including an N-terminal lectin-like domain (TEM1 domain 1. TEM1 D1), a sushi-like domain (TEM1D2), a three-repeated epidermal growth factor (EGF)-like domain (TEM1D3), a mucin-like domain (TEM1D4), a transmembrane domain (TEM1D5), and a cytoplasmic domain (TEM1D6). Recent reports have shown that TEM1 knockout mice exhibited a reduction in tumor growth, invasiveness and metastasis of colorectal xenografts compared with wild type mice. It has also been demonstrated that TEM1 facilitates tumor growth and inflammatory arthritis via its cytoplasmic domain. These results suggest that TEM1 plays a role in physiological and pathological conditions.